On March 26, 2021 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (Nasdaq:SGEN) reported that a marketing authorization application (MAA) for enfortumab vedotin was accepted by the European Medicines Agency (EMA) (Press release, Astellas, MAR 26, 2021, View Source [SID1234577178]). The MAA requests review of enfortumab vedotin for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. If approved, enfortumab vedotin would be the first antibody-drug conjugate (ADC) available in the European Union for people living with urothelial cancer.

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Enfortumab vedotin will be reviewed under accelerated assessment, which means the EMA’s Committee for Medicinal Products for Human Use (CHMP) can reduce the timeframe for evaluation.

The MAA is based on the global phase 3 EV-301 trial, which evaluated enfortumab vedotin versus chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. Results from the trial, which had a primary endpoint of overall survival for patients treated with PADCEV versus chemotherapy, were published in the New England Journal of Medicine.

"In the European Union, it is estimated that 118,000 people are diagnosed with urothelial cancer each year, and 52,000 die as a result of the disease," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "People with advanced urothelial cancer face an urgent need for new treatment options, which is reflected in the CHMP’s decision to grant accelerated assessment. We will continue to work with the CHMP toward our goal of securing marketing authorization as soon as possible."

About Urothelial Cancer

Urothelial cancer is the most common type of bladder cancer (90 percent of cases), and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.1 Globally, approximately 549,000 new cases of bladder cancer and 200,000 deaths are reported annually.2 In Europe, it is estimated that 118,000 patients are diagnosed with this form of cancer and 52,000 deaths are reported annually.3

Locally advanced and metastatic urothelial cancer is an aggressive disease that is associated with poor survival and high healthcare costs.4 Five-year relative survival rates for metastatic disease are estimated to be approximately 7 percent.5

About the EV-301 Trial

The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician’s choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based therapies. The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.6

About Enfortumab Vedotin

Enfortumab vedotin is an antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.7,8 Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).8

PADCEV (enfortumab vedotin-ejfv) U.S. Important Safety Information

Warnings and Precautions

Skin reactions: Severe cutaneous adverse reactions, including fatal cases of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later.

Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement.

Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines as clinically indicated. Withhold PADCEV and consider referral for specialized care for severe (Grade 3) skin reactions, suspected SJS, or TEN. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis, in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.

Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

Infusion site extravasation: Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

Embryo-fetal toxicity: PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

Adverse Reactions

Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

Lab Abnormalities

In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).

Drug Interactions

Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

Specific Populations

Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

For more information, please see the full Prescribing Information for PADCEV here.

About the Astellas and Seagen Collaboration

Astellas and Seagen Inc. are co-developing enfortumab vedotin under a 50:50 worldwide development and commercialization collaboration. In the United States, Astellas and Seagen co-promote enfortumab vedotin under the brand name PADCEV (enfortumab vedotin-ejfv). In the Americas outside the US, Seagen holds responsibility for commercialization activities and regulatory filings. Outside of the Americas, Astellas holds responsibility for commercialization activities and regulatory filings.

On March 25, 2021 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with cancer, reported a business update and reports financial results for the quarter and full year ended December 31, 2020 (Press release, Panbela Therapeutics, MAR 25, 2021, View Source [SID1234583755]). Management is hosting an earnings call today at 4:30 p.m. ET.

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The fourth quarter and full year 2020 was marked by meaningful corporate, financial and clinical progress.

2020 and Recent Highlights

Appointed Garry A. Weems, PharmD as its VP of Clinical Development and Medical Affairs
Entered into a research agreement with the Johns Hopkins University School of Medicine
Completing SBP-101’s enrollment in its Phase 1b trial
Uplisted to Nasdaq Capital Market
Closed $10.5 Million Public Offering
New CEO appointed on July 15, 2020
Fast Track designation received for SBP-101
"2020 was a year of significant accomplishments for SBP-101 and Panbela as a public company. In 2021 we are focused on continued execution of our pancreatic cancer program and expanding our addressable market opportunity outside of pancreatic cancer," said Jennifer K. Simpson, PhD, MSN, CRNP President & Chief Executive Officer of Panbela Therapeutics. "Last year’s achievements included securing fast track designation for SB1-101 in 1L metastatic pancreatic cancer, completing Phase 1b trial enrollment, strengthening our leadership team, firming up our balance sheet and uplisting to Nasdaq."

Dr. Simpson continued, "This year we are focused on leveraging 2020’s successes to execute on upcoming SBP-101 milestones in pancreatic cancer. We are also committed to expanding our total addressable market beyond pancreatic cancer. In support of that goal, we have appointed Garry A. Weems, PharmD as VP of Clinical Development and Medical Affairs, and entered into a research agreement with the Johns Hopkins University School of Medicine. We look forward to ongoing preclinical work yielding data in the second half of the year to inform future development pathways across tumors outside of pancreatic cancer as well as the potential combination with checkpoint inhibitors."

Based on interim data from our Phase I trial, SBP-101 demonstrated a 62% objective response rate in combination with gemcitabine & abraxane (G&A); more than double the historical standard of care for metastatic pancreatic cancer with G&A.

We believe SBP-101 has the potential to expand into other cancers with known elevated levels of polyamine metabolism.

Upcoming Milestones

Public release of data from phase 1 trial (targeting 1H’21)
Conference presentations (targeting 1H’21 or 2H’21)
Initiation of randomized phase 2 study (targeting mid-Year 21)
Public release of preclinical data across tumors outside of pancreatic cancer (targeting 2H’21)
Fourth Quarter ended December 31, 2020 Financial Results

General and administrative expenses were $0.9 million in the fourth quarter of 2020, compared to $0.5 million in the fourth quarter of 2019. The change in the third quarter is due primarily to increased headcount, and increased costs associated with our Nasdaq listing.

Research and development expenses were $0.7 million in the fourth quarter of 2020, down from $0.8 million in the fourth quarter of 2019. The change in the fourth quarter is due the lower manufacturing costs of our active ingredient offset in part by higher clinical trial costs and salaries.

Net loss in the fourth quarter of 2020 was $0.9 million, or $0.90 per diluted share, compared to a net loss of $1.0 million, or $0.15 per diluted share, in the fourth quarter of 2019.

Total cash was $9.0 million as of December 31, 2020. Total current assets were $9.8 million and current liabilities were $1.4 million as of the same date. The company had no debt as of December 31, 2020.

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To participate in this event, dial approximately 5 to 10 minutes before the beginning of the call.

The call will also be available over the Internet and accessible at: View Source

About SBP-101

SBP-101 is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. The molecule has shown signals of tumor growth inhibition in clinical studies of US and Australian metastatic pancreatic cancer patients, suggesting potential complementary activity with an existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, SBP-101 has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Recently observed serious visual adverse evets are being evaluated and the FDA has issued a partial clinical hold for the impacted study, pending Panbela’s evaluation and response. The safety data and PMI profile observed in the current Panbela sponsored clinical trial generally provides potential support for continued evaluation of the compound in a randomized clinical trial, subject to Panbela’s submission of a complete response and the FDA’s removal of the partial clinical hold. For more information, please visit View Source

On March 25, 2021 Processa Pharmaceuticals, Inc. (Nasdaq: PCSA) ("Processa" or the "Company"), a clinical stage company developing drugs for patients who have unmet medical conditions that require better treatment options to improve a patient’s survival and/or quality of life, reported that financial results for the year ended December 31, 2020, and provides corporate update (Press release, Processa Pharmaceuticals, MAR 25, 2021, View Source [SID1234578943]).

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Dr. David Young, CEO and chairman of Processa, commented, "2020 was a transformational year for our company; we in-licensed three exciting programs with potential markets exceeding $1 billion for each drug, improved our balance sheet, strengthened our management team and Board, up-listed to Nasdaq, and prepared the foundation for successful execution for our three clinical stage programs. I am delighted to report that we anticipate the first patients to be dosed with PCS6422 and PCS499 in the second quarter of 2021 with interim data for PCS6422 near the end of Q3 and for PCS499 in the first quarter of 2022."

Recent Highlights and New Developments

Selected 5 U.S. clinical sites to enroll patients with ulcerative necrobiosis lipoidica for our Phase 2B trial "A Randomized, Double-blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of PCS499 in Treating Ulcerations in Patients who Have Necrobiosis Lipoidica." Two to three additional clinical sites will be selected in the future including sites outside the U.S.
Entered into an exclusive licensing agreement with Elion Oncology, Inc. to develop, manufacture and commercialize PCS6422 (eniluracil) globally. PCS6422 is an oral drug to be administered with fluoropyrimidine cancer drugs (e.g., capecitabine, 5-FU). PCS6422 is designed to decrease the breakdown of the cancer drugs, which, without such intervention, reduce to inactive metabolites or metabolites that are known to cause unwanted side effects and to interfere with the anticancer activity.
Entered into a licensing agreement with Yuhan Corporation, a publicly traded South Korean company, to license PCS12852, a small molecule drug in development for the treatment of gastroparesis and functional gastrointestinal motility disorders.
Entered into a licensing agreement with Aposense LTD to license PCS11T, a pro-drug of SN38, the active metabolite of the widely used cancer drug irinotecan, that deposits SN38 in the membranes of cancer cells preferentially over normal cells.
Appointed Dr. Khalid Islam to the Company’s board of directors.
Appointed Michael Floyd as the Company’s chief operating officer.
Uplisted to Nasdaq.
Closed an underwritten public offering of 4,800,000 shares of common stock for a price to the public of $4.00 per share with net proceeds of $17.1 million.
In February 2021 we closed a private placement with institutional and accredited investors for $10.2 million. We sold 1,321,132 shares of the common stock at a purchase price of $7.75 per share for $10.2 million in the private placement and received net proceeds of $9.9 million.
Upcoming Clinical Drug Development Milestones

First half of 2021

Phase 1B First Patient Dosed: PCS6422 (Cancer)
Phase 2 First Patient Dosed: PCS499 (Ulcerative NL)
Second half of 2021

FDA IND Submission: PCS12852 (GI/Gastroparesis)
Interim Cohort Results Begin: PCS6422
First half of 2022

• Interim Results: PCS499

• Phase 2A First Patient Dosed: PCS12852

Financial Results for the Year Ended December 31, 2020

General and administrative expenses were $3.3 million compared to $1.6 million for the year ended December 31, 2019. The increase in our general and administrative expenses was primarily due to stock-based compensation.

Research and development expenses totaled $3.2 million compared to $2.3 million for the year ended December 31, 2019.

We also recorded $8.7 million dollars of costs as the acquisition of in-process research and development related to licensing agreements we executed for PCS6422, PCS12852 and PCS11T. A total of $8.6 million of this amount was non-cash consideration.

Our net loss was $14.4 million, compared to a net loss of $3.4 million for the year ended December 31, 2019. During 2020 we recorded non-cash expenses of $8.6 million for acquired in-process research and development and $2.7 million of stock-based compensation costs.

As of December 31, 2020, the Company had cash and cash equivalents of $15.4. In February 2021, we closed a $10.2 million private placement receiving net proceeds of $9.9 million.

Following the close of the offering and related transactions the Company will have 15.5 million common shares outstanding.

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On March 25, 2021 Herantis Pharma Plc ("Herantis"), an innovative clinical stage biotech company pioneering new disease modifying and regenerative biologic and gene therapies, reported the annual report for 2020 (Press release, Herantis Pharma, MAR 25, 2021, View Source,c3313818 [SID1234577485]). The Annual Report contains financial statements and the report of the Board of Directors. The Annual Report is available in PDF format in Finnish and English as appendices to this release and on Herantis Pharma’s website: View Source

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On March 25, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that COSELA (trilaciclib) has been added to two updated National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines): the Treatment Guidelines for Small Cell Lung Cancer and the Supportive Care Guidelines for Hematopoietic Growth Factors (Press release, G1 Therapeutics, MAR 25, 2021, View Source [SID1234577359]). These guidelines document evidence-based, consensus-driven management to ensure that all patients receive preventive, diagnostic, treatment, and supportive services that are most likely to lead to optimal outcomes.

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The NCCN Guidelines incorporate real-time updates in keeping with the rapid advancements in the field of cancer research and management. The development of these guidelines is an ongoing and iterative process based on a critical review of the best available evidence and derivation of recommendations by a multidisciplinary panel of experts in the field of cancer.

"The inclusion of COSELA in these NCCN guidelines is critical, as they are the standard resource for determining best course of treatment and supportive care for people living with cancer, and as such will enable healthcare providers to make informed decisions when treating patients with small cell lung cancer," said Raj Malik, M.D., Chief Medical Officer of G1 Therapeutics. "COSELA is an innovative product; it is the first and only proactive multilineage myeloprotection agent for use in extensive stage small cell lung cancer. We welcome the rapid and simultaneous inclusion in both updated guidelines which reinforces COSELA’s clinical utility and importance to patients."

The NCCN guidelines are made available free of charge to clinical professionals in the United States and internationally. In addition, patient resources including user-friendly versions of NCCN guidelines are available to patients and their families. For more information, visit View Source

About COSELA (trilaciclib)

COSELATM (trilaciclib) is the first and only myeloprotection therapy to help decrease the incidence of chemotherapy-induced myelosuppression. Administered intravenously as a 30-minute infusion within four hours prior to the start of chemotherapy, COSELA helps proactively deliver multilineage myeloprotection to patients with extensive-stage small cell lung cancer (ES-SCLC) being treated with chemotherapy. COSELA is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for ES-SCLC.

About Small Cell Lung Cancer

In the United States, approximately 30,000 small cell lung cancer patients are treated annually. SCLC, one of the two main types of lung cancer, accounts for about 10% to 15% of all lung cancers. SCLC is an aggressive disease and tends to grow and spread faster than NSCLC. It is usually asymptomatic; once symptoms do appear, it often indicates that the cancer has spread to other parts of the body. About 70% of people with SCLC will have cancer that has metastasized at the time they are diagnosed. The severity of symptoms usually increases with increased cancer growth and spread. From the time of diagnosis, the general 5-year survival rate for people with SCLC is 6%. The five-year survival rates for limited-stage (the cancer is confined to one side of the chest) SCLC is 12% to 15%, and for extensive stage (cancer has spread to the other lung and beyond), survival rates are less than 2%. Chemotherapy is the most common treatment for ES-SCLC.

COSELA(trilaciclib) for Injection

INDICATION

COSELA is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATION

COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib.

WARNINGS AND PRECAUTIONS

Injection-Site Reactions, Including Phlebitis and Thrombophlebitis

COSELA administration can cause injection-site reactions, including phlebitis and thrombophlebitis, which occurred in 56 (21%) of 272 patients receiving COSELA in clinical trials, including Grade 2 (10%) and Grade 3 (0.4%) adverse reactions. Monitor patients for signs and symptoms of injection-site reactions, including infusion-site pain and erythema during infusion. For mild (Grade 1) to moderate (Grade 2) injection-site reactions, flush line/cannula with at least 20 mL of sterile 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP after end of infusion. For severe (Grade 3) or life-threatening (Grade 4) injection-site reactions, stop infusion and permanently discontinue COSELA. Injection-site reactions led to discontinuation of treatment in 3 (1%) of the 272 patients.

Acute Drug Hypersensitivity Reactions

COSELA administration can cause acute drug hypersensitivity reactions, which occurred in 16 (6%) of 272 patients receiving COSELA in clinical trials, including Grade 2 reactions (2%). Monitor patients for signs and symptoms of acute drug hypersensitivity reactions. For moderate (Grade 2) acute drug hypersensitivity reactions, stop infusion and hold COSELA until the adverse reaction recovers to Grade £1. For severe (Grade 3) or life-threatening (Grade 4) acute drug hypersensitivity reactions, stop infusion and permanently discontinue COSELA.

Interstitial Lung Disease/Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin-dependent kinases (CDK)4/6 inhibitors, including COSELA, with which it occurred in 1 (0.4%) of 272 patients receiving COSELA in clinical trials. Monitor patients for pulmonary symptoms of ILD/pneumonitis. For recurrent moderate (Grade 2) ILD/pneumonitis, and severe (Grade 3) or life-threatening (Grade 4) ILD/pneumonitis, permanently discontinue COSELA.

Embryo-Fetal Toxicity

Based on its mechanism of action, COSELA can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use an effective method of contraception during treatment with COSELA and for at least 3 weeks after the final dose.

ADVERSE REACTIONS

Serious adverse reactions occurred in 30% of patients receiving COSELA. Serious adverse reactions reported in >3% of patients who received COSELA included respiratory failure, hemorrhage, and thrombosis.

Fatal adverse reactions were observed in 5% of patients receiving COSELA. Fatal adverse reactions for patients receiving COSELA included pneumonia (2%), respiratory failure (2%), acute respiratory failure (<1%), hemoptysis (<1%), and cerebrovascular accident (<1%).

Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received COSELA. Adverse reactions leading to permanent discontinuation of any study treatment for patients receiving COSELA included pneumonia (2%), asthenia (2%), injection-site reaction, thrombocytopenia, cerebrovascular accident, ischemic stroke, infusion-related reaction, respiratory failure, and myositis (<1% each).

Infusion interruptions due to an adverse reaction occurred in 4.1% of patients who received COSELA.

The most common adverse reactions (³10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.

DRUG INTERACTIONS

COSELA is an inhibitor of OCT2, MATE1, and MATE-2K. Co-administration of COSELA may increase the concentration or net accumulation of OCT2, MATE1, and MATE-2K substrates in the kidney (e.g., dofetilide, dalfampridine, and cisplatin).

To report suspected adverse reactions, contact G1 Therapeutics at 1-800-790-G1TX or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.